Synthetic bone substitutes must be biocompatible, osteoconductive, and mechanically compatible with native bone in order to be successfully used in clinical settings. Further improvement of the material is achieved by more rapid bone ingrowth and even stimulation of bone forming capacity of the body, or bone induction. This property of the implant material refers to its capacity to induce osteogenesis, or the mechanism that triggers stem cells to differentiate into bone-forming osteoblasts.
Osteoinduction is reported primarily for a subgroup of calcium phosphate ceramics, including hydroxyapatite (HA), β-tricalcium phosphate (β-TCP), biphasic calcium phosphate (BCP), that designates the mixture of HA and TCP, dicalcium phosphate anhydrous (DCPA), dicalcium phosphate dihydrate (DCPD), carbonated apatite, calcium pyrophosphates (CPP) and HA/calcium carbonate (CC) mixtures. Despite a thorough analysis of the materials described so far as osteoinductive, it is still not possible to describe how exactly an osteoinductive material should be designed and produced. All that is clear is that osteoinductive capacity can best be determined by heterotopic implantation, i.e. implantation in the tissues or organs where bone does not naturally grow, such as by ectopic implantation (i.e. intramuscular implantation or subcutaneous implantation).
In general, certain porous calcium phosphates have been found to exhibit osteoinductivity. For instance, Yamasaki et al., in Biomaterials 13:308-312 (1992), describe the occurrence of heterotopic ossification (formation of new bone in tissue that does not normally ossify) around porous hydroxyapatite ceramic granules, but not around dense granules. The porous granules range in size from 200 to 600 μm, and have a continuous and interconnected microporosity of which the pores range in diameter from 2 to 10 μm.
U.S. Pat. No. 6,511,510 describes a biocompatible and biodegradable calcium phosphate that exhibits improved osteoinductivity over the porous hydroxyapatite granules of Yamasaki et al. The biodegradable calcium phosphate has a total porosity of 20 to 90%, and encompasses both macropores ranging in size from 0.05 to 1.5 mm, as well as micropores ranging in size from 0.05 to 20 μm. The biodegradable calcium phosphate material is produced by mould casting and blocks can subsequently be granulated or cut to smaller size particles. The material, when implanted, is suitable to function as a (temporary) substitute for bone.
Despite the availability of the above materials, it would be advantageous if biomaterials for use in connection with living tissues could be provided with even better osteoconductive and osteoinductive properties, i.e. that result in even faster and more profound bone formation. It would also be advantageous if such osteoinductive materials could be easily introduced in the body of the mammal, most preferably such that they provide an easily implantable and effective scaffold material for the production of new bone in both osseous and non-osseous sites. Such material would be of much use for the production of de novo autologous bone, which might subsequently be used as bone substitute for repairing large bone defects.